The present research proposal represents our plans for a chemical investigation of the subtribe Melampodiinae (Compositae, Heliantheae), a group of plants with limited phytochemical data available. In the course of our sampling of chemical constituents of the genera Melampodium, Silphium, Clibadium, Desmanthodium and Ichtyothere, we will isolate and determine the structures, configurations and conformations of new and novel natural products, in particular sequiterpene lactones, which we encounter by the use of modern physical and chemical methods. A major aspect of our investigations is oriented toward a directed search for cytotoxic natural products, possible sesquitepene lactones from selected populations of Melampodium, the crude extracts of which show considerable antileukemic activity. The structure - cytotoxicity relationships of the newly isolated active natural products will help understand better the significance of various structural features in relation to the biological activity. Futhermore, our new phytochemical data will indirectly help solve biochemical systematic problems at the tribal, generic, species and populational levels.